CERTAIN PROBLEMS IN THE BIOCHEMICAL 

 STUDY OF DISEASE 



DeWITT STETTEN, Jr., National Institute of Arthritis and 

 Metabolic Diseases, National Institutes of Health, Bethesda, Maryland 



The study of normal metabolic processes may be pursued 

 with profit at many levels of biological organization, or, more 

 precisely, of biological disorganization. The investigator may 

 elect to employ the minimally disturbed intact animal, the iso- 

 lated perfused organ or tissue of that animal, the sliced, teased, 

 or minced preparation of such a tissue, the cell-free homogenate, 

 or the solution of enzyme or enzymes. Each level, as here listed, 

 represents a further degree of disorganization of an initially highly 

 integrated system, and the disorganization is in each case im- 

 posed by the experimenter. At each successive level of dis- 

 organization something is gained in the form of greater simplicity, 

 greater control over variables, greater facility in establishing the 

 necessary components of the system or reaction under scrutiny. 

 However, at each successive level of disorganization something 

 of importance is also lost. 



It may be worth while to consider briefly what is lost as 

 one proceeds with this dissection, first surgical and then chemical, 

 of the intact organism. As an example, the functioning of the 

 liver in situ is influenced by the normally continuous supply of 

 substrates, the normally continuous removal of products of its 



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